Multi-omics data integration reveals the molecular network of dysregulation IQGAP2-mTOR promotes cell proliferation

• Published in: Human cell : official journal of Human Cell Research Society Vol. 36; no. 4; pp. 1429 - 1440
• Main Authors: Chen, Tao, Fan, Xijie, Li, Guibin, Meng, Yuhuan
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.07.2023; Springer Nature B.V
• Subjects: AKT protein; Biomedical and Life Sciences; Cell Biology; Cell proliferation; Gynecology; Life Sciences; Oncology; Phosphorylation; Proteomes; Reproductive Medicine; Research Article; Signal transduction; Stem Cells; Surgery; TOR protein; Transcriptomes; Tumor cell lines; Tumor suppressor genes; Tumors; Cell proliferation; mTOR; Regulation networks; Multi-omics; IQGAP2
• ISSN: 1749-0774; 0914-7470; 1749-0774
• DOI: 10.1007/s13577-023-00912-8

IQGAP2 as a tumor suppressor gene can influence cell proliferation in multiple tumor cell lines. However, the regulation network of cell proliferation resulting solely from the deficiency of IQGAP2 in cells was still unclear. Here, we integrated transcriptome, proteome, and phosphoproteome analyses to investigate the regulatory network of cell proliferation in IQGAP2 knockdown HaCaT and HEK293 cells. Our findings revealed that the dysregulation of the IQGAP2-mTOR molecular network led to increased cell proliferation. We demonstrated that IQGAP2 knockdown enhanced the phosphorylation levels of AKT and S6K, leading to increased cell proliferation. Additionally, we found that AKT and mTOR inhibitors partially rescued abnormal cell proliferation by reducing hyperphosphorylation. Our data suggest a potential connection between the mTOR signaling pathway and aberrant cell proliferation in IQGAP2 knockdown cells. These findings offer a new therapeutic strategy for patients with IQGAP2 deficiency.